Bu derlemede, pandemi süresince dünya genelinde yoğun bakım ünitesinde takip edilen COVID-19 hastaların tedavi ve bakım süreçlerine ilişkin güncel bilgiler ve yaklaşımlara yer verilerek en önemli noktaların vurgulanması amaçlanmıştır.
📌 3 Key Takeaways
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Objective & Hypothesis:COVID-19 hastaları, gelişen şiddetli akut solunum sıkıntısı sendromuna bağlı olarak, solunum desteği yaklaşımlarının yanı sıra gelişen ciddi organ disfonksiyonlarına bağlı, yoğun bakım ünitesinde organ destek sistemlerine gereksinim duymaktadırlar.
📊
Key Findings & Data:Yoğun bakım ünitesinde çalışan sağlık profesyonellerinin, özellikle bulaş riski yüksek olan koronavirüs hastalığına yönelik infeksiyon kontrolü önlemlerine öncelik vererek hastaların tedavi ve bakım sürecini sürdürmeleri oldukça önem kazanmıştır.
💡
Conclusion & Impact:Bu derlemede, pandemi süresince dünya genelinde yoğun bakım ünitesinde takip edilen COVID-19 hastaların tedavi ve bakım süreçlerine ilişkin güncel bilgiler ve yaklaşımlara yer verilerek en önemli noktaların vurgulanması amaçlanmıştır.
🔬Design:Review & Systematic Survey
📍Scope:19 hasta
⚙️Variables:Koronavirüs · COVID-19 · SARS CoV-2
Özet
COVID-19 hastaları, gelişen şiddetli akut solunum sıkıntısı sendromuna bağlı olarak, solunum desteği yaklaşımlarının yanı sıra gelişen ciddi organ disfonksiyonlarına bağlı, yoğun bakım ünitesinde organ destek sistemlerine gereksinim duymaktadırlar. Yoğun bakım ünitesinde çalışan sağlık profesyonellerinin, özellikle bulaş riski yüksek olan koronavirüs hastalığına yönelik infeksiyon kontrolü önlemlerine öncelik vererek hastaların tedavi ve bakım sürecini sürdürmeleri oldukça önem kazanmıştır. Bu derlemede, pandemi süresince dünya genelinde yoğun bakım ünitesinde takip edilen COVID-19 hastaların tedavi ve bakım süreçlerine ilişkin güncel bilgiler ve yaklaşımlara yer verilerek en önemli noktaların vurgulanması amaçlanmıştır.
Kebapçı, A. (2020). COVID-19 Hastaların Yoğun Bakım Ünitelerinde Tedavi ve Bakım Girişimlerine İlişkin Güncel Yaklaşımlar. Yoğun Bakım Hemşireliği Dergisi, Cilt: 24 Sayı: EK-1 Özel Sayı, 46–56. https://ajindex.com/articles/1578278
Dünya Sağlık Örgütü (DSÖ) (2020). WHO Coronavirus Disease (COVID-19) Dashboard, https://covid19.who.int, Erişim tarihi: 20.05.2020
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506
Wu Z., Mcgoogan J. M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama 2020, 323.13: 1239-1242
Guan, Wei-jie, et al. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine, 2020, 382.18: 1708-1720
Halaclı B., Kaya, Akin; İskit, A. Critically ill COVID-19 patient. Turkish Journal of Medical Sciences 2020, 50.SI-1: 585-591
Vergano M., Bertolini G., Giannini A., Gristina G. R., Livigni S., Mistraletti,G.,. & Petrini, F. Clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances: the Italian perspective during the COVID-19 epidemic 2020, 24:165 9. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020
Liu Y., Yan L. M., Wan L., Xiang T. X., Le A., Liu J. M., & Zhang W. Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases 2020
Lescure F. X., Bouadma L., Nguyen D., Parisey M., Wicky P. H., Behillil S., & Enouf V. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. The Lancet Infectious Diseases 2020
Zou L., Ruan F., Huang M., Liang L., Huang H., Hong Z., & Guo Q. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. New England Journal of Medicine 2020; 382.12: 1177-1179
Brewster D. J., Chrimes N. C., Do T. B., Fraser K., Groombridge C. J., Higgs, A., & Nickson C. P. Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group. Med J Aust 2020, 16
Miller G. A., Buck C. R., Kang C. S., Aviles J. M., Younggren B. N., Osborn S., & Keay C. R. COVID‐19 in Seattle—Early lessons learned. Journal of the American College of Emergency Physicians Open 2020; 1(2), 85-91
Türk Yoğun Bakım Hemşireleri Derneği. (2020). Yoğun Bakım Ünı̇tesı̇nde Görev Alacak Hemşı̇reler İçı̇n Kaynak Kı̇tapçık Covıd-19 Pandemı̇sı̇’ne Özel, https://tybhd.org.tr/wp-content/uploads/2020/04/TYBHD_COVID19_Kitapçık-11.04.2020.pdf, erişim tarihi: 15.05.2020 17. Gattinoni L., Chiumello D., Caironi P., Busana M., Romitti F., Brazzi L., & Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes?. Intensive care medicine 2020, 1
Alhazzani W., Møller M. H., Arabi, Y. M., Loeb M., Gong M. N., Fan E.,. & Du B. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive care medicine 2020; 1-34 19. Weingart S. (2020). COVID Airway Management Thoughts, https://emcrit.org/emcrit/covid-airway-management/, Erişim tarihi;: 20.04.2020
Caı H., Chen Y., Chen Z., Fang Q., Han W., Hu S., Lı Ji., Lı T., Lu X., Qu T., Shen Y., Sheng J., Wang H., Weı G., Xu K., Zhao X., Zhong Z., Zhou J. COVID-19 Önleme ve Tedavi El Kitabı, 2020
American Association Critical-Care Nurses (AACN). Good V., Luehrs P. AACN Continous End-Tidal Carbon Dioxide Monitoring, AACN Procedure Manual for Critical Care (Debra Lynn, McHale Wigand), Saunders, 2017; 105-110
Cook T. M., El‐Boghdadly K., McGuire B., McNarry A. F., Patel A., & Higgs A. Consensus guidelines for managing the airway in patients with COVID‐19: Guidelines from the Difficult Airway Society, the Association of Anaesthetists the Intensive Care Society, the Faculty of Intensive Care Medicine and the Royal College of Anaesthetists. Anaesthesia 2020
Grasselli, G., Zangrillo, A., Zanella, A., Antonelli, M., Cabrini, L., Castelli, A., & Iotti, G. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. Jama 2020; 323(16): 1574-1581
Munshi L, Del Sorbo L, Adhikari NKJ, Hodgson CL, Wunsch H, Meade MO, Uleryk E, Mancebo J, Pesenti A, Ranieri VM, Fan E. Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 2017;14:280–288 25. Guérin C., Reignier J., Richard J. C., Beuret P., Gacouin A., Boulain T., & Clavel M. PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368(23):2159-2168
Nyren S, Radell P, Lindahl SG, Mure M, Petersson J, Larsson SA, Jacobsson H, Sanchez-Crespo A. Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated healthy volunteers. Anesthesiology 2010; 112:682–687 27. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8(5): 475-481
Elharrar X., Trigui Y., Dols A. M., Touchon F., Martinez S., Prud’homme E., & Papazian L. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. Jama 2020
Taccone P., Pesenti A., Latini R., Polli F., Vagginelli F., Mietto C., & Mancebo J. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. Jama 2009;18: 1977-1984 30. Ding L., Wang L., Ma W., & He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Critical care 2020; 24.1: 28
Scaravilli V., Grasselli G., Castagna L., Zanella A., Isgrò S., Lucchini A., & Pesenti A. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: a retrospective study. Journal of critical care 2015; 30(6): 1390-1394
Longhini F., Bruni A., Garofalo E., Navalesi P., Grasselli G., Cosentini R., & Vitale F. Helmet Continuous Positive Airway Pressure and prone positioning: a proposal for an early management of COVID-19 patients. Pulmonology 2020
Lucchini A., Bambi S., Mattiussi E., Elli S., Villa L., Bondi H., & Foti G. Prone Position in Acute Respiratory Distress Syndrome Patients: A Retrospective Analysis of Complications. Dimensions of Critical Care Nursing 2020, 39.1: 39-46
Girard R., Baboi L., Ayzac L., Richard J. C., Guérin C., & Proseva Trial Group. The impact of patient positioning on pressure ulcers in patients with severe ARDS: results from a multicentre randomised controlled trial on prone positioning. Intensive care medicine, 2014, 40.3: 397-403
Kim RS, Mullins K. Preventing facial pressure ulcers in acute respiratory distress syndrome (ARDS). J Wound Ostomy Continence Nurs 2016;43:427–429
Macdonald SPJ, Keijzers G, Taylor DM, Kinnear F, Arendts G, Fatovich DM, et al. Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial. Intensive Care Med 2018;44(12):2070-8
Cinel I, Kasapoglu US, Gul F, Dellinger RP. The initial resuscitation of septic shock. J Crit Care 2020;57:108-17
Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, Fruhwald S, Hiesmayr M, Ichai C, Jakob SM, Loudet CI, Malbrain ML, Montejo Gonzalez JC, Paugam-Burtz C, Poeze M, Preiser JC, Singer P, van Zanten AR, De Waele J, Wendon J, Wernerman J, Whitehouse T, Wilmer A, Oudemans-van Straaten HM, Function EWGoG (2017) Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med 43:380–398 42. Preiser JC, Chiolero R, Singer P. Yoğun Bakımda Beslenme Desteği, Modül, Nütrisyon Yolları, http://www.yogunbakimdergisi.org/managete/fu_folder/2006-EK/html/2006-6-Ek-1-057-068.htm, Erişim tarihi: 29.04.2020 43. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research 2020
Phua J, Weng L, Ling L, Egi M, Lim CM et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respiratory Medicine 2020
Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19 [published online ahead of print March 19, 2020]. Kidney Int.
Naicker S., Yang C. W., Hwang S. J., Liu B. C., Chen J. H., & Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney International 2020; 97(5): 824-828
American Society of Nephrology (ASN). Recommendations on the care of hospitalized patients with COVID-19 and kidney failure requiring renal replacement therapy. https://www. asn-online.org/g/blast/files/AKI_COVID-19_Recommendations_ Document_03.21.2020.pdf. Erişim tarihi: 30.04. 2020
Durvasula R., Wellington T., McNamara E., & Watnick S. COVID-19 and Kidney Failure in the Acute Care Setting: Our Experience From Seattle. American Journal of Kidney Diseases 2020
Ören B., Zengın Neriman. Yoğun Bakım Ünitelerindeki Akut Böbrek Yetmezliği ve Renal Replasman Tedavisinde Hemşirelik Yönetimi. Yoğun Bakım Hemşireliği Dergisi 2017; 21(2): 42-49
Dünya Sağlık Örgütü (DSÖ) (2020). WHO Coronavirus Disease (COVID-19) Dashboard, https://covid19.who.int, Erişim tarihi: 20.05.2020
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506
Wu Z., Mcgoogan J. M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama 2020, 323.13: 1239-1242
Guan, Wei-jie, et al. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine, 2020, 382.18: 1708-1720
Halaclı B., Kaya, Akin; İskit, A. Critically ill COVID-19 patient. Turkish Journal of Medical Sciences 2020, 50.SI-1: 585-591
Vergano M., Bertolini G., Giannini A., Gristina G. R., Livigni S., Mistraletti,G.,. & Petrini, F. Clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances: the Italian perspective during the COVID-19 epidemic 2020, 24:165 9. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020
Liu Y., Yan L. M., Wan L., Xiang T. X., Le A., Liu J. M., & Zhang W. Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases 2020
Lescure F. X., Bouadma L., Nguyen D., Parisey M., Wicky P. H., Behillil S., & Enouf V. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. The Lancet Infectious Diseases 2020
Zou L., Ruan F., Huang M., Liang L., Huang H., Hong Z., & Guo Q. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. New England Journal of Medicine 2020; 382.12: 1177-1179
Brewster D. J., Chrimes N. C., Do T. B., Fraser K., Groombridge C. J., Higgs, A., & Nickson C. P. Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group. Med J Aust 2020, 16
Miller G. A., Buck C. R., Kang C. S., Aviles J. M., Younggren B. N., Osborn S., & Keay C. R. COVID‐19 in Seattle—Early lessons learned. Journal of the American College of Emergency Physicians Open 2020; 1(2), 85-91
Türk Yoğun Bakım Hemşireleri Derneği. (2020). Yoğun Bakım Ünı̇tesı̇nde Görev Alacak Hemşı̇reler İçı̇n Kaynak Kı̇tapçık Covıd-19 Pandemı̇sı̇’ne Özel, https://tybhd.org.tr/wp-content/uploads/2020/04/TYBHD_COVID19_Kitapçık-11.04.2020.pdf, erişim tarihi: 15.05.2020 17. Gattinoni L., Chiumello D., Caironi P., Busana M., Romitti F., Brazzi L., & Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes?. Intensive care medicine 2020, 1
Alhazzani W., Møller M. H., Arabi, Y. M., Loeb M., Gong M. N., Fan E.,. & Du B. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive care medicine 2020; 1-34 19. Weingart S. (2020). COVID Airway Management Thoughts, https://emcrit.org/emcrit/covid-airway-management/, Erişim tarihi;: 20.04.2020
Caı H., Chen Y., Chen Z., Fang Q., Han W., Hu S., Lı Ji., Lı T., Lu X., Qu T., Shen Y., Sheng J., Wang H., Weı G., Xu K., Zhao X., Zhong Z., Zhou J. COVID-19 Önleme ve Tedavi El Kitabı, 2020
American Association Critical-Care Nurses (AACN). Good V., Luehrs P. AACN Continous End-Tidal Carbon Dioxide Monitoring, AACN Procedure Manual for Critical Care (Debra Lynn, McHale Wigand), Saunders, 2017; 105-110
Cook T. M., El‐Boghdadly K., McGuire B., McNarry A. F., Patel A., & Higgs A. Consensus guidelines for managing the airway in patients with COVID‐19: Guidelines from the Difficult Airway Society, the Association of Anaesthetists the Intensive Care Society, the Faculty of Intensive Care Medicine and the Royal College of Anaesthetists. Anaesthesia 2020
Grasselli, G., Zangrillo, A., Zanella, A., Antonelli, M., Cabrini, L., Castelli, A., & Iotti, G. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. Jama 2020; 323(16): 1574-1581
Munshi L, Del Sorbo L, Adhikari NKJ, Hodgson CL, Wunsch H, Meade MO, Uleryk E, Mancebo J, Pesenti A, Ranieri VM, Fan E. Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 2017;14:280–288 25. Guérin C., Reignier J., Richard J. C., Beuret P., Gacouin A., Boulain T., & Clavel M. PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368(23):2159-2168
Nyren S, Radell P, Lindahl SG, Mure M, Petersson J, Larsson SA, Jacobsson H, Sanchez-Crespo A. Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated healthy volunteers. Anesthesiology 2010; 112:682–687 27. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8(5): 475-481
Elharrar X., Trigui Y., Dols A. M., Touchon F., Martinez S., Prud’homme E., & Papazian L. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. Jama 2020
Taccone P., Pesenti A., Latini R., Polli F., Vagginelli F., Mietto C., & Mancebo J. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. Jama 2009;18: 1977-1984 30. Ding L., Wang L., Ma W., & He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Critical care 2020; 24.1: 28
Scaravilli V., Grasselli G., Castagna L., Zanella A., Isgrò S., Lucchini A., & Pesenti A. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: a retrospective study. Journal of critical care 2015; 30(6): 1390-1394
Longhini F., Bruni A., Garofalo E., Navalesi P., Grasselli G., Cosentini R., & Vitale F. Helmet Continuous Positive Airway Pressure and prone positioning: a proposal for an early management of COVID-19 patients. Pulmonology 2020
Lucchini A., Bambi S., Mattiussi E., Elli S., Villa L., Bondi H., & Foti G. Prone Position in Acute Respiratory Distress Syndrome Patients: A Retrospective Analysis of Complications. Dimensions of Critical Care Nursing 2020, 39.1: 39-46
Girard R., Baboi L., Ayzac L., Richard J. C., Guérin C., & Proseva Trial Group. The impact of patient positioning on pressure ulcers in patients with severe ARDS: results from a multicentre randomised controlled trial on prone positioning. Intensive care medicine, 2014, 40.3: 397-403
Kim RS, Mullins K. Preventing facial pressure ulcers in acute respiratory distress syndrome (ARDS). J Wound Ostomy Continence Nurs 2016;43:427–429
Macdonald SPJ, Keijzers G, Taylor DM, Kinnear F, Arendts G, Fatovich DM, et al. Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial. Intensive Care Med 2018;44(12):2070-8
Cinel I, Kasapoglu US, Gul F, Dellinger RP. The initial resuscitation of septic shock. J Crit Care 2020;57:108-17
Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, Fruhwald S, Hiesmayr M, Ichai C, Jakob SM, Loudet CI, Malbrain ML, Montejo Gonzalez JC, Paugam-Burtz C, Poeze M, Preiser JC, Singer P, van Zanten AR, De Waele J, Wendon J, Wernerman J, Whitehouse T, Wilmer A, Oudemans-van Straaten HM, Function EWGoG (2017) Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med 43:380–398 42. Preiser JC, Chiolero R, Singer P. Yoğun Bakımda Beslenme Desteği, Modül, Nütrisyon Yolları, http://www.yogunbakimdergisi.org/managete/fu_folder/2006-EK/html/2006-6-Ek-1-057-068.htm, Erişim tarihi: 29.04.2020 43. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research 2020
Phua J, Weng L, Ling L, Egi M, Lim CM et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respiratory Medicine 2020
Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19 [published online ahead of print March 19, 2020]. Kidney Int.
Naicker S., Yang C. W., Hwang S. J., Liu B. C., Chen J. H., & Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney International 2020; 97(5): 824-828
American Society of Nephrology (ASN). Recommendations on the care of hospitalized patients with COVID-19 and kidney failure requiring renal replacement therapy. https://www. asn-online.org/g/blast/files/AKI_COVID-19_Recommendations_ Document_03.21.2020.pdf. Erişim tarihi: 30.04. 2020
Durvasula R., Wellington T., McNamara E., & Watnick S. COVID-19 and Kidney Failure in the Acute Care Setting: Our Experience From Seattle. American Journal of Kidney Diseases 2020
Ören B., Zengın Neriman. Yoğun Bakım Ünitelerindeki Akut Böbrek Yetmezliği ve Renal Replasman Tedavisinde Hemşirelik Yönetimi. Yoğun Bakım Hemşireliği Dergisi 2017; 21(2): 42-49